Visiting Speakers

Moriah Thomason, Ph.D. - Associate Professor
Departments of Child and Adolescent Psychiatry and Population Health
New York University School of Medicine

 Jan 23, 2019 @ 3:00 p.m.

 Medical Center | Adolph Lower Aud (1-7619)

Host: Del Monte Institute for Neuroscience and Dept. of Neuroscience

Mark Bear, PhD - Investigator of the Howard Hughes Medical Institute
Picower Professor of Neuroscience in The Picower Institute for Learning and Memory
Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology

 Feb 25, 2019 @ 4:00 p.m.

 Medical Center | K-307 (3-6408)

Steven Petersen, Ph.D. - The James S. McDonnell Professor of Cognitive Neuroscience in Neurology
Professor of Neuroscience, Biomedical Engineering, Psychological & Brain Sciences, and Radiology
Washington University

 Mar 14, 2019 @ 4:00 p.m.

 Medical Center | 1-9576 Ryan Case Method Auditorium

Host: Univ. Rochester School of Medicine and Dentistry, the Del Monte Institute for Neuroscience, and Dept. of Neuroscience

Staci Bilbo, PhD - Director of Research, Lurie Center for Autism
Harvard University Program in Neuroscience

 Apr 01, 2019 @ 4:00 p.m.

 Medical Center | K-307 (3-6408)

Jeffrey Macklis, MD - Harvard Department of Stem Cell and Regenerative Biology

 Apr 22, 2019 @ 4:00 p.m.

 Medical Center | K-307 (3-6408)

Michael Proulx, PhD - Associate Professor of Psychiatry, Department of Psychiatry University of Bath, Bath, United Kingdom

 Oct 07, 2019 @ 9:30 a.m.

Spatial knowledge is key for most everything we do. The study of spatial cognition is now able to take advantage of advances in computational modelling, Virtual Reality and Augmented Reality with important implications for theory and application. I will explore these issues through a few case studies of our research, including: the use of eye-tracking with interactive virtual environments; virtual reality to explore multisensory perception; and using motion-tracking and augmented reality to assess the presentation of visual information in tactile or auditory displays to the blind or blindfolded. These immersive technologies hold great potential for advancements in fundamental and translational neuroscience.

 Medical Center | Class of ’62 Auditorium

Niccolo Terrando, D.I.C., Ph.D. - Associate Professor in Anesthesiology
Assistant Research Professor in Cell Biology
Duke University Medical Center

 Oct 28, 2019 @ 4:00 p.m.

Perioperative neurocognitive disorders (PND), including acute postoperative delirium and longer-lasting postoperative cognitive dysfunction, are quintessential geriatric complications that affects up to 60% of older adults (1). Orthopedic surgery is a routine procedure in frail and elderly patients, often resulting in high incidence of PND, thus contributing to adverse events and poorer outcomes. To understand the pathophysiology of these complications we have developed a clinically relevant mouse model of orthopedic surgery consisting of an intramedullary fixation of the tibia under general anesthesia to evaluate the impact of aseptic trauma on the central nervous system (2). Using this model we uncovered a link between peripheral cytokines and neuroinflammation in leading to cognitive deficits (3-5). We also identified the role of blood-brain barrier opening and macrophage infiltration as being pivotal for the development of postoperative neuroinflammation and ensuing hippocampal-dependent memory dysfunction (6). Harnessing inflammatory-resolving pathways, for example via cholinergic modulation or specialized pro-resolving lipid mediators, dampen glia activation in response to surgical trauma and curtail the cognitive decline that follows (7-8). Similar pathological hallmarks of blood-brain barrier opening, monocytic infiltration in the cerebrospinal fluid, and microglia reactivity are now observed in patients after non-neurological surgery (9). This suggests a possible role, and putative targeting, of these processes in the pathogenesis of PND.

 Medical Center | K-207 (2-6408)

Oliver Bracko, Ph.D. - Postdoctoral Associate
Meinig School for Biomedical Engineering
Cornell University

 Dec 02, 2019 @ 1:30 p.m.

It has been known for decades that Alzheimer’s Disease (AD) patients and AD mouse models display reduced cerebral blood flow (CBF). Using in vivotwo-photon imaging, we recently identified the cellular mechanism that underlies this hypoperfusion. We found that neutrophils transiently adhere to the endothelial cell wall in about 2% of capillaries in the APP/PS1 mouse model of AD, plugging blood flow in those capillary segments (0.4% in wild-type mice). Blocking this adhesion using an antibody against a neutrophil surface protein increased CBF in APP/PS1 mice to near wild-type levels and led to a rapid improvement in cognitive function. The molecular drivers that link amyloid-beta pathology to this capillary plugging remain unknown. Here, we report that inhibiting NOX2-containing NAPDH-oxidase, a reactive oxygen species producing enzyme shown to be activated in APP/PS1 mice, for two weeks with a small peptide, gp91 ds –tat, decreased the fraction of capillaries with stalled blood flow by 67%, increased CBF by 29%, and improved performance on object replacement and y-maze spatial memory tasks. A scrambled version of the peptide inhibitor did not lead to any of these changes. This study implicates the NOX2 pathway as a new molecular mechanism underlying capillary stalling and CBF reductions APP/PS1 mice and could represent a molecular pathway with potential therapeutic opportunities for AD.

 Medical Center | 1-9576 Case Method Room

Host: Department of Neuroscience - Faculty Search Committee

Alexander Nott, Ph.D - Project Scientist
Department of Cellular & Molecular Medicine
University of California, San Diego

 Dec 09, 2019 @ 9:30 a.m.

Long-lasting changes in gene expression are mediated by ‘epigenetic’ adaptations in chromatin structure; these modifications orchestrate gene expression programs that guide cell-type-specific responses to environmental signals. My research explores how cell-type-specific epigenetic mechanisms drive brain physiology in health and disease. My early work demonstrated that histone deacetylase 2 (HDAC2), an epigenetic eraser, is negatively regulated by nitric oxide signaling in primary neurons. Further, I showed that nitric oxide-mediated inhibition of HDAC2 is required for activation of gene expression programs critical for normal mouse brain development. Next, I studied Rett syndrome, a brain disorder caused by mutations in MeCP2. I found that neuronal loss of HDAC3, a binding partner of MeCP2, elicits Rett syndrome-associated behaviors in mice. Contrary to the idea that HDAC3 functions as an epigenetic eraser, I found that HDAC3 activated gene expression through regulation of the FOXO transcription factors. My current research explores the function of noncoding DNA variants associated with brain-related disease-risk at gene regulatory regions called enhancers. I generated promoter-enhancer interactome maps that connect noncoding disease-risk variants to target genes in the major cell types of the brain. These datasets revealed that genetic variants associated with increased risk of Alzheimer’s disease (AD) were largely confined to microglia enhancers, whereas genetic variants for psychiatric disorders were enriched in neuronal enhancers. Additionally, I identified a microglia-specific enhancer at the BIN1 locus that harbors AD-risk variants; BIN1 is an AD-risk gene that has largely been studied in neurons. Deletion of the microglia-specific BIN1 enhancer substantially reduced BIN1 expression in microglia and not in neurons or astrocytes. Overall, this work has revised the gene repertoire influenced by noncoding AD-risk variants and has revealed the likely cell types in which they function.
Refreshments

 Medical Center | K307 (3-6407)

Host: Department of Neuroscience - Faculty Search Committee